This invention relates to a process for removal of methamphetamine from benzphetamine hydrochloride thereby providing highly pure benzphetamine hydrochloride by means of a convenient liquid extraction process employing an organic solvent and water.
The production of benzphetamine has been known for a considerable period of time and was disclosed in U.S. Pat. No. 2,789,138 to Heinzelman et al. The chemical name of the physioacitve material, benzphetamine, is d-N-methyl-N-benzyl-beta-phenylisopropylamine. According to that patent benzyl chloride is reacted with methamphetamine in the presence of a base, typically sodium carbonate. The reaction is typically carried out in a non-reactive organic solvent such as benzene, toluene, xylene or the like. The product is recovered by mixing the reaction mixture with water, extracting with solvent, then converting the benzphetamine to the hydrochloride by addition of hydrochloric acid. The thus produced acid salt is then fractionally distilled under vacuum at temperatures in the range of from about 155° C. to about 165° C. to obtain the amine. Such purification process has several disadvantages including the exposure of the product to high temperatures, and the need for expensive vacuum pumps and a vacuum still to achieve the desired reduced pressure.
The impurity of most concern in the process for preparing benzphetamine hydrochloride is methamphetamine. It is self-evident that any pharmaceutical should be as pure as possible and that such a drug as methamphetamine be eliminated to the extent economically feasible.
Extraction of methamphetamine has been the subject of research in the prior art. An activated methamphetamine is shown in U.S. Pat. No. 5,976,812. The activated methamphetamine is in a class of derivatives of very active materials, typically methamphetamine-p-carboxybutyl-maleinimidoethylamide. In the purification process for this type of compound, the derivative is shaken with sodium hydroxide in water forming oil which is extracted three times with toluene. U.S. Pat. No. 4,056,922 discloses that methamphetamine can be extracted at either pH 2 or pH 9 with concentrating agent selected from silica gel and kieslguhr.
While there are numerous purification schemes available on an analytical basis to remove materials such as methamphetamine, a convenient large-scale production method to provide highly pure benzphetamine hydrochloride substantially free of methamphetamine is not commercially available other than by vacuum distillation. A convenient, large-scale method to provide benzphetamine hydrochloride has not been heretofore available.